Inactive n-acetylated-alpha-linked acidic dipeptidase-like protein 2 (naaladl2) as a therapeutic and diagnostic target

Abstract

The present invention provides methods and compositions for treatment, screening, diagnosis and prognosis of cancer, such as prostate cancer, bladder cancer, breast cancer, esophagus cancer, head and neck cancer, colorectal cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, uterus cancer and pancreatic cancer, for monitoring the effectiveness of cancer, such as prostate cancer, bladder cancer, breast cancer, esophagus cancer, head and neck cancer, colorectal cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, uterus cancer and pancreatic cancer treatment, and for drug development.

1 - 28 . (canceled) 
     
     
         29 . A method for the treatment of cancer wherein NAALADL2 is expressed by cells of the cancer, which comprises administering to a subject in need thereof a therapeutically effective amount of an affinity reagent which binds to NAALADL2. 
     
     
         30 . The method according to  claim 29 , wherein the cancer is selected from the group consisting of prostate cancer, bladder cancer, breast cancer, esophagus cancer, head and neck cancer, colorectal cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, uterus cancer and pancreatic cancer. 
     
     
         31 . The method according to  claim 29 , wherein the affinity reagent binds specifically to NAALADL2. 
     
     
         32 . The method according to  claim 29 , wherein the affinity reagent is an antibody or a functional fragment thereof or an antibody mimetic. 
     
     
         33 . The method according to  claim 32 , wherein the affinity reagent is a monoclonal antibody an antigen-binding fragment thereof, a chimeric antibody, a human antibody, a humanized antibody, a single chain antibody, a defucosylated antibody or a bispecific antibody. 
     
     
         34 . The method according to  claim 32 , wherein:
 (a) the functional antibody fragment is a UniBody, a domain antibody or a Nanobody; or   (b) the antibody mimetic is an Affibody, a DARPin, an Anticalin, an Avimer, a Versabody or a Duocalin.   
     
     
         35 . A method for the treatment of prostate cancer wherein NAALADL2 is expressed by cells of the prostate cancer, which comprises administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody which binds to NAALADL2 and CD3. 
     
     
         36 . The method according to  claim 29 , wherein the affinity reagent contains or is conjugated to a therapeutic moiety. 
     
     
         37 . The method according to  claim 36 , wherein the therapeutic moiety is a cytotoxic moiety or a radioactive isotope. 
     
     
         38 . The method according to  claim 36 , wherein the affinity reagent is an antibody drug conjugate. 
     
     
         39 . The method according to  claim 29 , wherein the affinity reagent elicits antibody-dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), and/or T-cell cytotoxicity. 
     
     
         40 . The method according to  claim 29 , wherein the affinity reagent induces apoptosis of cancer cells, kills or reduces the number of cancer stem cells and/or kills or reduces the number of circulating cancer cells. 
     
     
         41 . A method of detecting, diagnosing and/or screening for or monitoring the progression of cancer wherein NAALADL2 is expressed by cells of the cancer, or of monitoring the effect of a cancer drug or therapy wherein NAALADL2 is expressed by cells of the cancer, in a subject which comprises detecting the presence or level of NAALADL2, or one or more fragments thereof, or the presence or level of nucleic acid encoding NAALADL2 or which comprises detecting a change in the level thereof in said subject or detecting the presence or level of antibodies capable of immunospecific binding to NAALADL2, or one or more fragments thereof. 
     
     
         42 . The method according to  claim 41  which comprises detecting the presence of NAALADL2, or one or more fragments thereof, or the presence of nucleic acid encoding NAALADL2, in which either (a) the presence of an elevated level of NAALADL2 or said one or more fragments thereof or an elevated level of nucleic acid encoding NAALADL2 in the subject as compared with the level in a healthy subject, or (b) the presence of a detectable level of NAALADL2 or said one or more fragments thereof or a detectable level of nucleic acid encoding NAALADL2 in the subject as compared with a corresponding undetectable level in a healthy subject is indicative of the presence of cancer wherein NAALADL2 is expressed in said cancer, in said subject. 
     
     
         43 . The method according to  claim 41 , wherein the presence of NAALADL2, or one or more fragments thereof, or the presence of nucleic acid encoding NAALADL2 or the presence or level of antibodies capable of immunospecific binding to NAALADL2, or one or more fragments thereof, is detected by analysis of a biological sample obtained from the subject. 
     
     
         44 . The method according to  claim 41 , wherein the presence of NAALADL2, or one or more fragments thereof, is detected using an affinity reagent which binds to NAALADL2. 
     
     
         45 . The method according to  claim 44 , wherein the affinity reagent contains or is conjugated to a detectable label. 
     
     
         46 . The method according to  claim 41 , wherein the cancer is selected from the group consisting of prostate cancer, bladder cancer, breast cancer, esophagus cancer, head and neck cancer, colorectal cancer, liver cancer, lung cancer, ovarian cancer, gastric cancer, uterus cancer and pancreatic cancer. 
     
     
         47 . The method according to  claim 29 , wherein the subject is a human. 
     
     
         48 . A method for identifying an agent for the treatment or prophylaxis of cancer wherein NAALADL2 is expressed by cells of the cancer, wherein the method comprises (a) contacting NAALADL2, or one or more fragments thereof, with a candidate agent; and (b) determining whether the agent binds to NAALADL2, or one or more fragments thereof.